Primary Immune Deficiency Diseases (PIDDs) include a group of rare diseases whose clinical manifestations encompass multiple clinical specialties. While great progress has been made in the molecular characterization of PIDDs, little is known of long-term outcome of the various forms. Development of comprehensive and collaborative Registries for PIDDs is of utmost importance to define outcomes and optimize clinical interventions in affected patients. In addition, there is a need to I\increase availability and sharing of the rare patient derived biological samples across the scientific community to facilitate efficient study of PIDDs. Finally, dedicated educational initiatives are essential to bring together specialists from different disciplines and create the next generation of physician experts who will care for PIDD patients and investigators who will make breakthroughs to increase our understanding of these disorders. As participants in the creation and development of the United States Immune Deficiency Network (USIDNET) we plan to capitalize on Its success in response to RFA-AI-08-066 to meet the following goals: Aim 1: Expand utilization of the existing USIDNET Registry and forge links with other existing Registries and networks with an interest in PIDD, including the Center for International Blood and Marrow Transplantation Research (CIBMTR), the Severe Chronic Neutropenia International Registries (SCNIR) and the Clinical and Translational Science Award (CTSA) sites that pursue activities in the PIDD community. We will develop new PIDD-specific forms, expand the data collected, and solicit participation through communication with physicians and advocacy groups. We will perform Quality of Life studies using validated instruments. We will define regional variability in diagnosis and treatment and make these data available to improve provider awareness and quality of care. Aim 2: Enlarge the current USIDNET Repository of cell lines, and create a Distributed Biobank to extend the availability of rare patient samples and unique reagents that can be collected at diverse sites and shared through facilitated collaborations. In conjunction with the CTSA Consortium we will build specific opportunities for sharing rare PIDD resources. Aim 3: Provide intensive training and educational opportunities to foster physician-scientist careers in PIDD and encourage collaborative translational research. We will develop educational materials for physicians in allied fields and establish new venues for building PIDD knowledge in the United States. RELEVANCE (See instructions): Primary immune defects, now numbering over 150 defects, have provided unique and unparalleled opportunities to study the individual cellular, biochemical and molecular events necessary for a functional human immune system. This program extends and amplifies three key resources established by the USIDNET, needed for the systematic study of these diseases: a Patient Registry, a Repository/Biobank and an educational program needed to sustain and carry out this work. These will accelerate work in immunology and will greatly benefit work in other diseases in which the immune system plays a integral role.